Pathophysiological role of cardiotrophin-1 in heart failure

心肌营养素-1在心力衰竭中的病理生理作用

• 批准号: 12670662
• 负责人: AOYAMA Takesh
• 金额: $ 2.05万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670662/
• 关键词: heart failure; myscardial infarction; hypertension; ventricular remodeling; cardiotrophin 1; gp130; カルジオトロフィン1; 心筋梗塞; カルジオトロフィン-1

Cardiotrophin-1 (CT-1) is a potent cytokine that stimulates the assembly of sarcomeric units in series in cardiomyocytes through gp130 signaling, resulting in myocardial cell hypertrophy. We examined the role of CT-1 and gp130 system in the two rat models of congestive heart failure. First, we examined the expression of CT-1 and gp130 in a rat model of myocardial infarction. Progressive left ventricular dilatation and inadequate hypertrophy of the surviving myocardium were confirmed by echocardiography. The densitometric analysis of RT-PCR revealed a significant increase in CT-1 and gp130 mRNA levels compared with those of the sham-operated rats at 1, 3, 7, 14, 28 and 56 days post-infarct in both ventricles. The protein levels of CT-1 and gp130, determined by Western blot analysis, were significantly increased compared to those of sham-operated rats, and peaked in the acute stage and declned thereafter in the three regions described above. Immunohistochemical staining showed that CT-1 … More and gp130-immunoreactivities were detected in cardiomyocytes and fibroblast-like cells. An augmented CT-1 and gp130 system thus seems to play an important role during ventricular remodeling after myocardial infarction. Secondly, we examined the expression of CT-1 and gp130 in Dahl salt-sensitive (DS) rats with a high-salt diet which showed a distinct transition from left ventricular hypertrophy (LVH) to congestive heart failure (CHF). The expression levels of CT-1 were significantly increased at the CHF stage compared with the LVH stage and age-matched Dahl salt-resistant (DR) rats (n=6 for each group). gp130 mRNA and protein levels DS rats at 11 and 17 weeks were significantly increased compared with age-matched DR rats. The isolated myocyte length of DS rats at 17 weeks was the longest among the 4 groups of rats. The left ventricular end-diastolic dimension (LVDd) of DS rats was significantly increased at the CHF stage. There was a significant correlation between the CT-1 protein level and LVDd. CT-1 may play a role in ventricular remodeling during transition from LVH to CHF in the rat hypertensive model. These findings in the two heart failure models strongly suggest that CT-1 plays a central role in the ventricular dilatation in heart failure. Less

心肌营养蛋白-1 (CT-1) 是一种有效的细胞因子，可通过 gp130 信号传导刺激心肌细胞中肌节单元的串联组装，导致心肌细胞肥大。我们检查了 CT-1 和 gp130 系统在两种充血性心力衰竭大鼠模型中的作用。首先，我们检测了心肌梗塞大鼠模型中 CT-1 和 gp130 的表达。超声心动图证实进行性左心室扩张和存活心肌不充分肥厚。 RT-PCR 光密度分析显示，梗死后 1、3、7、14、28 和 56 天，与假手术大鼠相比，双侧心室 CT-1 和 gp130 mRNA 水平显着增加。通过蛋白质印迹分析测定，与假手术大鼠相比，CT-1和gp130的蛋白水平显着升高，并在急性期达到峰值，此后在上述三个区域中下降。免疫组织化学染色显示，在心肌细胞和成纤维细胞样细胞中检测到 CT-1 和 gp130 免疫反应性。因此，增强的 CT-1 和 gp130 系统似乎在心肌梗塞后心室重塑过程中发挥着重要作用。其次，我们检测了高盐饮食的 Dahl 盐敏感 (DS) 大鼠中 CT-1 和 gp130 的表达，显示从左心室肥厚 (LVH) 到充血性心力衰竭 (CHF) 的明显转变。与LVH期和同龄Dahl耐盐(DR)大鼠相比，CHF期CT-1的表达水平显着升高(每组n=6)。与同龄DR大鼠相比，第11周和第17周时DS大鼠的gp130 mRNA和蛋白水平显着升高。 17周时DS大鼠的离体肌细胞长度是4组大鼠中最长的。 DS大鼠的左心室舒张末期内径（LVDd）在CHF阶段显着增加。 CT-1蛋白水平与LVDd呈显着相关性。 CT-1可能在大鼠高血压模型从LVH向CHF转变过程中的心室重塑中发挥作用。两种心力衰竭模型中的这些发现强烈表明，CT-1 在心力衰竭的心室扩张中发挥着核心作用。较少的

项目成果

Yoshitaka Iwanaqa, Yasuki Kihara, Takeshi Yoneda, Takeshi Aoyama, Shigetake Sasayama: "Modulation of in vivo cardiac hypertrophy.with insulin-like growth factor-1 and angiotensin-converting enzyme inhibitor : relationship between change in myosin isoform

Yoshitaka Iwanaqa、Yasuki Kihara、Takeshi Yoneda、Takeshi Aoyama、Shigetake Sasayama：“用胰岛素样生长因子-1 和血管紧张素转换酶抑制剂调节体内心脏肥大：肌球蛋白亚型变化之间的关系

Y.Takimoto et al.: "Differential expression of three types of nitric oxide synthase in both infarcted and non-infarcted left ventricles after myocardial infarction in the rat"Int. J. Cardiol. 76. 135-145 (2000)

Y.Takimoto 等人：“大鼠心肌梗塞后梗塞和非梗塞左心室中三种类型一氧化氮合酶的差异表达”Int。

Yoshihito Takimoto, Takeshi Aovama, Yoshitaka Iwanaga, Toshiaki Izumi, Yasuki Kihara, Shigetake Sasayama: "Increased expression of cardiotrophin-1 and gp130 during ventricular remodeling in hypertensive rats"Am. J. Physiol.. Vol. 282. H896-H901 (2002)

Yoshihito Takimoto、Takeshi Aovama、Yoshitaka Iwanaga、Toshiaki Izumi、Yasuki Kihara、Shigetake Sasayama：“高血压大鼠心室重构过程中心肌营养素-1 和 gp130 的表达增加”Am。

T.Aoyama et al.: "Augmented expression of cardiac trophin-1 and its receptor component, gp130, in both left and right ventricles after myocardial infarction in the rat"J.Moll.Cell.Cardiol.. 32. 1821-1830 (2000)

T.Aoyama 等人：“大鼠心肌梗死后左心室和右心室中心脏 tropin-1 及其受体成分 gp130 的增强表达”J.Moll.Cell.Cardiol.. 32. 1821-1830（

Y.Takimoto et al.: "Differential expression of three types of nitric oxide synthase in both the infarcted and non-infarcted left ventricle after myocardial infarction in the rat"Int. J. Cardiol.. 76. 135-145 (2000)

Y.Takimoto 等人：“大鼠心肌梗塞后梗塞和非梗塞左心室中三种类型一氧化氮合酶的差异表达”Int。